The recent studies showed that many small molecules have the inhibitory activity of NF-κ B, such as salicylanilide and aspirin. The mechanism would strongly affect the inhibition of osteoclastogenesis. In other natural compounds, such as Paeonol from Paeonia lactiflora Pallas, Ikarisoside A from Epimedium koreanum, Bavachalcone from Psoralea corylifolia, etc., could inhibit osteoclastogenesis. Besides, Indeno[1,2-c]quinoline derivatives, Benzopyranyl Tetracycles derivatives and 3-Amino-2-hydroxypropoxyisoflavone derivatives are also found have the inhibition ability. However, the mechanism and effect is still unclear. Therefore, synthesizing more compounds, which can be applied to inhibit osteoclastogenesis, could have a potent to inhibit the development of anti-osteoporosis drugs.
In the bone regeneration process, once the balance of the bone remodeling is broken, the bone resorption of the osteoclasts is dominated over bone formation of the osteoblasts, the bone remodeling would be imbalanced. As a result, osteocytes, osteopenia and bone mineral density are decreased, and then induce lots of bone diseases, such as osteoporosis, periodontitis or osteoarthritis.
The osteoclasts are developed from hematopoietic precursor cells. Further, the Macrophage-Colony Stimulating Factor (M-CSF) and Receptor Activator of Nuclear factor Kappa B Ligand (RANKL) are secreted by osteoblast. They can combine with the c-Fms and RANK on the cell membrane of the osteoclast precursor cells, and then induce the secretion of tartrate-resistant acid phosphatase (TRAP), integrin β3 expression, and actin ring formation, etc. These proteins enhance the osteoclasts motility and adhere on the bone surface. In addition, the expression of cathepsin K matrix metalloproteinase-9 (MMP-9), dendritic cell-specific transmembrane protein (DC-STAMP), ATPase, H+ transporting lysosomal V0 subunit D2 (ATP6V0D2) also induce the osteoclast precursor cells into the matured (diameter is 20-100 mm) multinucleated cells (MNCs) (containing 4-20 nucleus), which have the bone resorption function. Besides, osteoblasts not only secret M-CSF and RANKL, which induce the osteocytes growth and differentiation, but also secret the osteoprotegerin (OPG). OPG is associated with RANKL to prevent the association of RANKL and RANK. Hence, it prevents and inhibits the formation of osteoclasts, decreases the bone resorption.